Mlvi-4 and Mlvi-1 are two putative oncogenes which are involved in the induction of T cell lymphomas by MoMuLV in rats and which map 25 and 300 kb 3'of Myc respectively. Their activation by provirus insertion in rat T cell lymphomas occurs in parallel with the activation of c-myc. The human homologues of these putative oncogenes are targeted frequently by chromosomal aberrations in a variety of human hematopoietic and nonhematopoietic neoplasms suggesting that they are involved either alone or in concert with c-myc in their induction. Recently, we identified and cloned the human homologues of these loci. Using these clones as probes, we have shown that the human MLVI-4 and MLVI-1 loci map in the same region relative to MYC as their rat homologues. In addition, using a human MLVI-4 probe we showed that similarly to its rat homologue the human MLVI-4 locus is transcriptionally active in the spleen. The experiments in this application will examine the role of the human MLVI-4 and MLVI-1 homologues in the induction of human tumors. More specifically these experiments will address the genetic organization, expression and function of these genes in both normal and neoplastic cells. To achieve these goals we will utilize standard recombinant DNA and tissue culture technology. Animal experiments will involve the inoculation of newborn mice with recombinant retroviruses.